Risk for non-insulindependent diabetes in the normoglycaemic elderly is associated with impaired cognitive function

Vanhanen, Matti; Koivisto, Keijo; Karjalainen, Leena; Helkala, Eeva‐Liisa; Laakso, Markku; Soininen, Hilkka; Riekkinen, Paavo

doi:10.1097/00001756-199704140-00041

Cited by 72 publications

(49 citation statements)

References 9 publications

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“…For example, improvements in diabetes control have been associated with improvements in cognitive functioning [19,20]. In addition, deficits in learning and memory have also been described among non-diabetic individuals with insulin resistance (for example [21,22]), even after accounting for the possible effects of atherosclerosis [23].…”

Section: Introductionmentioning

confidence: 99%

Hippocampal damage and memory impairments as possible early brain complications of type 2 diabetes

et al. 2007

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Aims/hypothesis There is evidence that type 2 diabetes mellitus is associated with cognitive impairment. Most studies investigating this association have evaluated elderly individuals, after many years of diabetes, who generally have poor glycaemic control and significant vascular disease. The aim of the current study was to investigate the early cognitive consequences and associated brain correlates of type 2 diabetes. Materials and methods With regard to cognition and brain measures, we compared 23 age-, sex-and educationmatched control subjects with 23 mostly middle-aged individuals with relatively well-controlled diabetes of less than 10 years from the time of diagnosis. Results We found deficits in hippocampal-based memory performance and preservation of other cognitive domains. Relative to control subjects, individuals with diabetes had reductions in brain volumes that were restricted to the hippocampus. There was an inverse relationship between glycaemic control and hippocampal volume; in multivariate regression analysis, HbA 1c was the only significant predictor of hippocampal volume, accounting for 33% of the observed variance. Other variables commonly associated with type 2 diabetes, such as elevated BMI, hypertension or dyslipidaemia, did not independently contribute to the variance in hippocampal volume. Conclusions/interpretation These results suggest that the medial temporal lobe may be the first brain site affected by type 2 diabetes and that individuals in poorer metabolic control may be affected to a greater extent.

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Section: Introductionmentioning

confidence: 99%

Hippocampal damage and memory impairments as possible early brain complications of type 2 diabetes

et al. 2007

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“…In addition, nondiabetic individuals with mild forms of impaired glucose tolerance (IGT) may also have cognitive impairments (7,8). The prevalence of memory problems and IGT rise with age (1, 9, 10).…”

mentioning

confidence: 99%

Reduced glucose tolerance is associated with poor memory performance and hippocampal atrophy among normal elderly

Convit

Wolf²,

Tarshish³

et al. 2003

Proc. Natl. Acad. Sci. U.S.A.

300

184

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Poor glucose tolerance and memory deficits, short of dementia, often accompanies aging. The purpose of this study was to ascertain whether, among nondiabetic, nondemented middle-aged and elderly individuals, poorer glucose tolerance is associated with reductions in memory performance and smaller hippocampal volumes. We studied 30 subjects who were evaluated consecutively in an outpatient research setting. The composition of the participant group was 57% female and 68.6 ؎ 7.5 years of age; the participants had an average education of 16.2 ؎ 2.3 years, a score on the Mini Mental State Examination of 28.6 ؎ 1.5, a glycosylated hemoglobin (HbA1C) of 5.88 ؎ 0.74%, and a body mass index of 24.9 ؎ 4.1 kg͞m 2 . Glucose tolerance was measured by an i.v. glucose tolerance test. Memory was tested by using the Wechsler Paragraphs recall tests at the time of administering the i.v. glucose tolerance test. The hippocampus and other brain volumes were measured by using validated methods on standardized MRIs. Decreased peripheral glucose regulation was associated with decreased general cognitive performance, memory impairments, and atrophy of the hippocampus, a brain area that is key for learning and memory. These associations were independent of age and Mini Mental State Examination scores. Therefore, these data suggest that metabolic substrate delivery may influence hippocampal structure and function. This observation may bring to light a mechanism for aging brain injury that may have substantial medical impact, given the large number of elderly individuals with impaired glucose metabolism.T wenty-five percent of individuals over 65 years of age have sufficient cognitive problems, short of dementia, to affect the quality of their lives (1, 2). The ability to learn consciously and recall new information, which is known as recent or declarative memory, is one of the areas most affected during aging. However, our knowledge about the medical factors that predispose a person to age-associated cognitive problems remains undeveloped.There is a growing literature indicating that individuals with diabetes have impairments in recent memory (3-6). In addition, nondiabetic individuals with mild forms of impaired glucose tolerance (IGT) may also have cognitive impairments (7,8). The prevalence of memory problems and IGT rise with age (1, 9, 10). In addition to genetic predisposition, obesity and low levels of physical activity have been identified as risk factors for IGT in adults and children (11,12). With life expectancy and obesity on the rise, the prevalence of memory dysfunction and IGT will likely continue to climb. However, it remains to be established whether there are associations between peripheral glucose regulation and memory performance among nondemented middleaged and elderly individuals.The hippocampus, a brain structure deep in the temporal lobe, is key for recent memory formation (13-15). Hypothalamuspituitary-adrenal axis hyperactivity have been associated with hippocampal atrophy in aging (16) and in Cushing's disease (1...

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“…Such studies would enable the investigation of connectivity between brain regions associated with memory processing such as the frontal gyrus and hippocampus, consolidating research already done in the area using fMRI [29]. Some studies have indicated that patients with DM2 have a longer P300 latency [35,38,39], although others have found no differences compared to healthy controls [40]. Importantly, strict glycaemic control has been shown to lead to improvements in P300 latency and potential memory enhancement [35,39].…”

Section: Dm2 and Functional Brain Imagingmentioning

confidence: 99%

Type 2 Diabetes and Memory: Using Neuroimaging to Understand the Mechanisms

Jones¹,

Riby²,

Mitchell³

et al. 2014

CDR

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Abstract:The most robust and frequently reported cognitive deficits in type 2 diabetes (DM2) are those that relate to memory. Behavioural research has identified a number of potential contributory physiological factors, including abnormalities in glucose metabolism, such as hyperglycaemia and hypoglycaemia. The impact of these mechanisms on memory has been further investigated through the use of both structural and functional neuroimaging. Structural brain imaging has indicated that memory impairments in DM2 are associated with global atrophy of the brain. Further data suggest that localised atrophy in the hippocampal area, a brain region critical to memory formation and consolidation, may be primarily responsible for the memory deficits seen in this population. Functional imaging data has corroborates these findings, with functional magnetic resonance imaging (fMRI) suggesting reduced connectivity between the hippocampus and surrounding brain regions, particularly the frontal and temporal gyri. Despite this, little functional neuroimaging research has directly investigated differences in regional brain activity between healthy and DM2 participants whilst memory tasks are being performed. By using neuroimaging techniques to their full potential, we can acquire a fuller, more comprehensive picture of the impact that DM2 has on memory.Keywords: Brain, cognition, EEG, memory, MRI, neuroimaging, type 2 diabetes.Type 2 diabetes (DM2) in older adults is associated with cognitive impairment, reflecting accelerated cognitive decline relative to that expected in normal ageing [1][2][3]. The most frequently reported and most robust deficits are seen in verbal episodic memory [4], although other domains of memory such as face recognition and working memory may also be affected [5,6]. However, it is still unclear whether these deficits reflect impairments in their encoding or retrieval. These memory impairments have been attributed to varied physiological mechanisms, including abnormalities in glucose metabolism, insulin resistance, dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis and vascular complications [7,8]. The role of these physiological mechanisms in neurocognitive functioning in individuals withDM2 has been investigated using a variety of neuroimaging techniques. Methods such as magnetic resonance imaging (MRI) and electroencephalography (EEG), have allowed researchers to examine both the structural and functional impact of DM2 on the brain. This review will consider these neuroimaging studies and speculate on how these innovative techniques could be informative in identifying underlying mechanisms of memory deficits in DM2. DM2 AND COGNITIVE IMPAIRMENT: THE MECHANISMSDisturbances in glucose metabolism, including hyperglycaemia and hypoglycaemia, have been associated with cognitive dysfunction [7,9]. Summerfield, Deary and Frier [7] observed that induced acute hyperglycaemia in adults with DM2 impaired cognitive performance, most notably in the working memory domain. Relatively few studies have inve...

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Risk for non-insulindependent diabetes in the normoglycaemic elderly is associated with impaired cognitive function

Cited by 72 publications

References 9 publications

Hippocampal damage and memory impairments as possible early brain complications of type 2 diabetes

Hippocampal damage and memory impairments as possible early brain complications of type 2 diabetes

Reduced glucose tolerance is associated with poor memory performance and hippocampal atrophy among normal elderly

Type 2 Diabetes and Memory: Using Neuroimaging to Understand the Mechanisms

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